<i>TP53</i>mutation in therapy-related myeloid neoplasm defines a distinct molecular subtype
Authors: Devendra Hiwase, Christopher Hahn, Elizabeth Ngoc Hoa Tran, Rakchha Chhetri, Anmol Baranwal, Aref Al-Kali, Kirsty Sharplin, Dariusz Ladon, Rachel Hollins, Patricia Greipp, Monika Kutyna, Hassan Alkhateeb, Talha Badar, Paul Wang, David M. Ross, Deepak Singhal, Naranie Shanmuganathan, Peter Bardy, Ashanka Beligaswatte, David Yeung, Mark R. Litzow, Abhishek Mangaonkar, Pratyush Giri, Cindy Lee, Angie Yong, Noemi Horvath, Nimit Singhal, Raghu Gowda, William Hogan, Naseema Gangat, Mrinal Patnaik, Kebede Begna, Ing S. Tiong, Andrew Wei, Sharad Kumar, Anna Brown, Hamish Scott, Daniel Thomas, Chung H. Kok, Ayalew Tefferi, Mithun Vinod Shah
Journal: Blood (2022)

Letter to Blood| March 2, 2023 TP53 mutation in therapy-related myeloid neoplasm defines a distinct molecular subtype Devendra Hiwase, Devendra Hiwase Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, AustraliaPrecision Medicine Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, AustraliaAdelaide Medical School, University of Adelaide, Adelaide, SA, AustraliaCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia https://orcid.org/0000-0002-6666-3056 Search for other works by this author on: This Site PubMed Google Scholar Christopher Hahn, Christopher Hahn Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, AustraliaGenetic and Molecular Pathology, SA Pathology, Adelaide, SA, Australia https://orcid.org/0000-0001-5105-2554 Search for other works by this author on: This Site PubMed Google Scholar Elizabeth Ngoc Hoa Tran, Elizabeth Ngoc Hoa Tran Precision Medicine Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, AustraliaAdelaide Medical School, University of Adelaide, Adelaide, SA, Australia https://orcid.org/0000-0003-1644-2287 Search for other works by this author on: This Site PubMed Google Scholar Rakchha Chhetri, Rakchha Chhetri Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, AustraliaPrecision Medicine Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, AustraliaAdelaide Medical School, University of Adelaide, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Anmol Baranwal, Anmol Baranwal Division of Hematology, Mayo Clinic, Rochester, MN Search for other works by this author on: This Site PubMed Google Scholar Aref Al-Kali, Aref Al-Kali Division of Hematology, Mayo Clinic, Rochester, MN https://orcid.org/0000-0002-0824-3715 Search for other works by this author on: This Site PubMed Google Scholar Kirsty Sharplin, Kirsty Sharplin Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Dariusz Ladon, Dariusz Ladon Genetic and Molecular Pathology, SA Pathology, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Rachel Hollins, Rachel Hollins Genetic and Molecular Pathology, SA Pathology, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Patricia Greipp, Patricia Greipp Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN https://orcid.org/0000-0002-5536-9011 Search for other works by this author on: This Site PubMed Google Scholar Monika Kutyna, Monika Kutyna Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, AustraliaPrecision Medicine Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, AustraliaAdelaide Medical School, University of Adelaide, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Hassan Alkhateeb, Hassan Alkhateeb Division of Hematology, Mayo Clinic, Rochester, MN Search for other works by this author on: This Site PubMed Google Scholar Talha Badar, Talha Badar Department of Hematology/Oncology, Mayo Clinic, Jacksonville, FL https://orcid.org/0000-0003-1548-918X Search for other works by this author on: This Site PubMed Google Scholar Paul Wang, Paul Wang ACRF Cancer Genomic Facility, SA Pathology, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar David M. Ross, David M. Ross Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, AustraliaPrecision Medicine Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, AustraliaAdelaide Medical School, University of Adelaide, Adelaide, SA, AustraliaCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia https://orcid.org/0000-0001-7171-2935 Search for other works by this author on: This Site PubMed Google Scholar Deepak Singhal, Deepak Singhal Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, AustraliaPrecision Medicine Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia https://orcid.org/0000-0002-2024-2969 Search for other works by this author on: This Site PubMed Google Scholar Naranie Shanmuganathan, Naranie Shanmuganathan Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, AustraliaPrecision Medicine Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia https://orcid.org/0000-0001-5895-8797 Search for other works by this author on: This Site PubMed Google Scholar Peter Bardy, Peter Bardy Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Ashanka Beligaswatte, Ashanka Beligaswatte Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar David Yeung, David Yeung Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, AustraliaPrecision Medicine Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Mark R. Litzow, Mark R. Litzow Division of Hematology, Mayo Clinic, Rochester, MN https://orcid.org/0000-0002-9816-6302 Search for other works by this author on: This Site PubMed Google Scholar Abhishek Mangaonkar, Abhishek Mangaonkar Division of Hematology, Mayo Clinic, Rochester, MN Search for other works by this author on: This Site PubMed Google Scholar Pratyush Giri, Pratyush Giri Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Cindy Lee, Cindy Lee Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Angie Yong, Angie Yong Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Noemi Horvath, Noemi Horvath Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Nimit Singhal, Nimit Singhal Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Raghu Gowda, Raghu Gowda Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar William Hogan, William Hogan Division of Hematology, Mayo Clinic, Rochester, MN Search for other works by this author on: This Site PubMed Google Scholar Naseema Gangat, Naseema Gangat Division of Hematology, Mayo Clinic, Rochester, MN https://orcid.org/0000-0002-9104-6172 Search for other works by this author on: This Site PubMed Google Scholar Mrinal Patnaik, Mrinal Patnaik Division of Hematology, Mayo Clinic, Rochester, MN https://orcid.org/0000-0001-6998-662X Search for other works by this author on: This Site PubMed Google Scholar Kebede Begna, Kebede Begna Division of Hematology, Mayo Clinic, Rochester, MN https://orcid.org/0000-0003-2730-8593 Search for other works by this author on: This Site PubMed Google Scholar Ing S. Tiong, Ing S. Tiong Department of Haematology, The Alfred Hospital and Monash University, Melbourne, VIC, Australia https://orcid.org/0000-0001-7417-4343 Search for other works by this author on: This Site PubMed Google Scholar Andrew Wei, Andrew Wei Department of Haematology, The Alfred Hospital and Monash University, Melbourne, VIC, Australia https://orcid.org/0000-0002-7514-3298 Search for other works by this author on: This Site PubMed Google Scholar Sharad Kumar, Sharad Kumar Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Australia https://orcid.org/0000-0001-7126-9814 Search for other works by this author on: This Site PubMed Google Scholar Anna Brown, Anna Brown Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, AustraliaGenetic and Molecular Pathology, SA Pathology, Adelaide, SA, Australia https://orcid.org/0000-0002-9023-0138 Search for other works by this author on: This Site PubMed Google Scholar Hamish Scott, Hamish Scott Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, AustraliaGenetic and Molecular Pathology, SA Pathology, Adelaide, SA, Australia https://orcid.org/0000-0002-5813-631X Search for other works by this author on: This Site PubMed Google Scholar Daniel Thomas, Daniel Thomas Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, AustraliaPrecision Medicine Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, AustraliaAdelaide Medical School, University of Adelaide, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Chung H. Kok, Chung H. Kok Precision Medicine Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, AustraliaAdelaide Medical School, University of Adelaide, Adelaide, SA, Australia Search for other works by this author on: This Site PubMed Google Scholar Ayalew Tefferi, Ayalew Tefferi Division of Hematology, Mayo Clinic, Rochester, MN Search for other works by this author on: This Site PubMed Google Scholar Mithun Vinod Shah Mithun Vinod Shah Division of Hematology, Mayo Clinic, Rochester, MN https://orcid.org/0000-0002-5359-336X Search for other works by this author on: This Site PubMed Google Scholar Blood (2023) 141 (9): 1087–1091. https://doi.org/10.1182/blood.2022018236 Article history Submitted: September 6, 2022 Accepted: December 8, 2022 Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Request Permissions Cite Icon Cite Search Site Citation Devendra Hiwase, Christopher Hahn, Elizabeth Ngoc Hoa Tran, Rakchha Chhetri, Anmol Baranwal, Aref Al-Kali, Kirsty Sharplin, Dariusz Ladon, Rachel Hollins, Patricia Greipp, Monika Kutyna, Hassan Alkhateeb, Talha Badar, Paul Wang, David M. Ross, Deepak Singhal, Naranie Shanmuganathan, Peter Bardy, Ashanka Beligaswatte, David Yeung, Mark R. Litzow, Abhishek Mangaonkar, Pratyush Giri, Cindy Lee, Angie Yong, Noemi Horvath, Nimit Singhal, Raghu Gowda, William Hogan, Naseema Gangat, Mrinal Patnaik, Kebede Begna, Ing S. Tiong, Andrew Wei, Sharad Kumar, Anna Brown, Hamish Scott, Daniel Thomas, Chung H. Kok, Ayalew Tefferi, Mithun Vinod Shah; TP53 mutation in therapy-related myeloid neoplasm defines a distinct molecular subtype. Blood 2023; 141 (9): 1087–1091. doi: https://doi.org/10.1182/blood.2022018236 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBlood Search Subjects: Myeloid Neoplasia TO THE EDITOR: Recent World Health Organization (WHO)1 classifications (5th edition), International Consensus Classification (ICC),2 and the European LeukemiaNet (ELN) guidelines3 included new categories for TP53-mutated (TP53mut) myeloid neoplasms (MNs) to acknowledge their uniformly poor outcomes and stimulate clinical research. However, there are critical differences in the details between these classifications, especially regarding single-hit TP53mut status, and their significance relating to therapy-related myeloid neoplasm (t-MN), a rare but often fatal malignancy diagnosed following exposure to cytotoxic therapies, remains unclear. Here, we report an international cohort consisting of t-MN with full characterization of TP53mut allele status and provide compelling evidence of poor outcome of TP53mut t-MN irrespective of the allelic status of TP53. The WHO defines a single category of myelodysplastic syndrome (MDS) with biallelic TP53 inactivation (MDS-biTP53)... References 1.Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022;36(7):1703-1719.Google ScholarCrossrefSearch ADS PubMed 2.Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022;140(11):1200-1228.Google ScholarCrossrefSearch ADS PubMed 3.Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and Management of AML in Adults: 2022 ELN Recommendations from an International Expert Panel. Blood. 2022;140(22):1345-1377.Google ScholarPubMed 4.Bernard E, Tuechler H, Greenberg Peter L, et al. Molecular International Prognostic Scoring System for Myelodysplastic Syndromes. NEJM Evidence. 2022;1(7):EVIDoa2200008.Google ScholarCrossrefSearch ADS 5.Bernard E, Nannya Y, Hasserjian RP, et al. Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes. Nat Med. 2020;26(10):1549-1556.Google ScholarCrossrefSearch ADS PubMed 6.Grob T, Al Hinai ASA, Sanders MA, et al. Molecular characterization of mutant TP53 acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2022;139(15):2347-2354.Google ScholarCrossrefSearch ADS PubMed 7.Weinberg OK, Siddon A, Madanat YF, et al. TP53 mutation defines a unique subgroup within complex karyotype de novo and therapy-related MDS/AML. Blood Adv. 2022;6(9):2847-2853.Google ScholarCrossrefSearch ADS PubMed © 2023 by The American Society of Hematology2023 © 2023 by The American Society of Hematology2023 You do not currently have access to this content. Sign in via your Institution